| 摘要: | 卵巢癌主要影響更年期後的女性，根據衛福部統計，每10萬人口約有7人死於卵巢癌。早期症狀通常不明顯，導致很多患者在診斷時已是晚期。第一期卵巢癌的存活率高達93％，但第四期存活率僅25％。卵巢位置使得在晚期，癌細胞可能經由腹膜轉移到腹腔，形成腹膜癌。癌症轉移是致命的過程，使病情難以控制，最終導致死亡。為了研究卵巢癌轉移到腹膜的微環境，使用了一個稱為TAH模型的方法並改良TAH模型，以模擬癌細胞的遠端轉移。改良後的TAH模型會將腹膜細胞株MeT-5A放置在上方，然後將卵巢癌細胞株SKOV-3放置在下方。結果顯示，在不含腹膜細胞的水膠晶片上，癌細胞的附著明顯少於含有腹膜細胞的組別。因此，TAH模型成功地模擬了人體癌細胞遠端轉移的機制。此外，還探討了一種名為PEDOT:PSS的導電聚合物，它具有高生物相容性和穩定性，目前已廣泛應用於生物傳感器以測量生物訊號。研究顯示，PEDOT: PSS具有高度可調控性，當與海藻酸鈉鹽水膠混合後，會改變表面特性，使細胞難以附著在水膠芯片上。為了研究卵巢癌細胞在轉移到腹腔時的附著情況，在海藻酸鈉鹽水膠芯片上使用了不同濃度的PEDOT: PSS，包括100mM、10mM、1mM、100μM、10μM、1μM和0.1μM。結果顯示，這些濃度都在不同程度上抑制了癌細胞的附著，但PEDOT: PSS除了100mM濃度外並未在做成海藻酸鈉鹽水膠芯片時對細胞造成毒性影響。在細胞毒性測試中PEDOT: PSS對於細胞有些微毒性IC50落在0.507mM。為了瞭解是否因加入PEDOT: PSS改變了水膠芯片親疏水性因此測試接觸角，發現所有的PEDOT: PSS海藻酸鈉鹽水膠芯片都是非常親水性。由於PEDOT: PSS具導電性，因此進行氧化還原電化學反應，發現PEDOT: PSS氧化態可以使歸巢的細胞更加貼附於PEDOT: PSS海藻酸鈉鹽水膠芯片。除此之外還測試表面帶電性，結果顯示無論是否加入PEDOT: PSS表面電位都為負電。這項研究採用 PEDOT: PSS 並修改了TAH模型來模擬腹膜微環境，可作為一種臨床前模型，用於防止癌細胞沾黏抑制癌症轉移的新方法。
Ovarian cancer primarily affects postmenopausal women. According to the Ministry of Health and Welfare statistics, about 7 out of every 100,000 people die from ovarian cancer. Early symptoms are usually not apparent, leading to many patients being diagnosed at a late stage. The survival rate for stage I ovarian cancer is as high as 93%, but the survival rate for stage IV is only 25%. The location of the ovaries means that in advanced stages, cancer cells can metastasize to the peritoneum, forming peritoneal cancer. Metastasis is a fatal process, making the disease difficult to control and ultimately leading to death. To study the microenvironment of ovarian cancer metastasis to the peritoneum, a modified TAH (Transwell-based alginate hydrogel) model was used to simulate the distant metastasis of cancer cells. In this modified TAH model, peritoneal cell line MeT-5A is placed at the top, and ovarian cancer cell line SKOV-3 is placed at the bottom. The results showed that cancer cell attachment was significantly lower on hydrogel chips without peritoneal cells compared to those with peritoneal cells, successfully simulating the mechanism of distant metastasis of human cancer cells. Additionally, a conductive polymer named PEDOT: PSS was explored for its high biocompatibility and stability. PEDOT: PSS is currently widely used in biosensors to measure biological signals. Studies have shown that PEDOT: PSS has high tunability and, when mixed with alginate hydrogel, changes surface properties, making it difficult for cells to adhere to the hydrogel chip. To study the adhesion of ovarian cancer cells when metastasizing to the peritoneal cavity, different concentrations of PEDOT: PSS were used on alginate hydrogel chips, including 100mM, 10mM, 1mM, 100μM, 10μM, 1μM, and 0.1μM. Results showed that these concentrations inhibited cancer cell adhesion to varying degrees, but apart from the 100mM concentration, PEDOT: PSS did not cause cytotoxic effects on the alginate hydrogel chip. PEDOT: PSS showed slight toxicity in cytotoxicity tests with an IC50 of 0.507mM. To understand if the addition of PEDOT: PSS altered the hydrophilicity or hydrophobicity of the hydrogel chip, contact angle tests were conducted, revealing that all PEDOT: PSS alginate hydrogel chips were highly hydrophilic. Due to the conductivity of PEDOT: PSS, redox electrochemical reactions were performed, showing that the oxidized state of PEDOT: PSS increased the adhesion of homing cells to the PEDOT: PSS alginate hydrogel chip. Furthermore, surface charge tests indicated that the surface potential was negative regardless of adding PEDOT: PSS. This study utilized PEDOT: PSS and modified the TAH model to simulate the peritoneal microenvironment. This approach can serve as a preclinical model for developing new methods to prevent cancer cell adhesion and inhibit cancer metastasis. |
